ABSTRACT There are not any scientifically proven or approved therapies for COVID-19. Convalescent plasma (CP), which is plasma that is obtained from people who have recovered from COVID-19, contains antibodies to SARS-CoV- 2, the virus that causes this disease. CP has a long and storied history of improving symptoms and mortality from other pandemic diseases, such as 1918 and 2009 influenza and SARS, as well as a myriad of other toxin- mediated and infectious diseases. Thus, CP is a rationally based and readily available therapeutic option for COVID-19. There are thousands of people who have recovered from COVID-19 in the New York City area who have donated their plasma to help others who are suffering from this disease. This project is a collaborative randomized blinded placebo-controlled trial to evaluate the efficacy of treatment with CP in hospitalized patients with COVID-19 that is being conducted at three New York University (NYU) Langone Health hospitals in Manhattan, Brooklyn and Long Island, Bellevue Hospital Center, and three Montefiore Medical Center (MMC) hospitals in the Bronx. We designed and launched this trial as the pandemic surged in NYC by rapidly developing a multicenter, well-powered Phase 2 trial via regional collaborations established by Einstein-Montefiore and NYU-Langone CTSAs with support from the New York Blood Center (NYBC). The hypothesis underpinning the trial is that compared to placebo, administration of CP will avert respiratory deterioration, the main cause of death in patients with COVID-19. The specific aims of this project are: 1) To examine whether CP decreases the likelihood of respiratory deterioration in patients hospitalized for COVID-19 compared to placebo (saline solution, SS) at 14 days from administration, and 2) To identify associations between quantitative and qualitative SARS- CoV-2 antibody levels and clinical outcomes in patients hospitalized for COVID-19 who receive CP and placebo. The public health benefit of proof of CP efficacy against COVID-19, which has already caused 338,000 infections and 21,845 deaths in the United States and 187,250 infections and 1,127 deaths in New York City would be a tremendous and public health advance that could save thousands of lives.